Dissolution Curves Research Articles

Dissolution Challenges Associated with the Surface pH of Drug Particles: Integration into Mechanistic Oral Absorption Modeling.

The present work aimed to differentiate between in vitro dissolution profiles of ibuprofen as input for GastroPlus™ and to see the impact on systemic exposure. In vitro dissolution profiles of ibuprofen obtained under low- and high-buffered dissolution media were used as input using the z-factor approach. In a second step, a customized surface pH calculator was applied to predict the surface pH of ibuprofen under these low- and high-buffered dissolution conditions. These surface pH values were adopted in GastroPlus™ and simulations were performed to predict the systemic outcome. Simulated data were compared with systemic data of ibuprofen obtained under fasted state conditions in healthy subjects. The slower dissolution rate observed when working under low-buffered conditions nicely matched with the slower dissolution rate as observed during the clinical aspiration study and was in line with the systemic exposure of the drug. Finally, a population simulation was performed to explore the impact of z-factor towards bioequivalence (BE) criteria (so-called safe space). Concerning future perspectives, the customized calculator should be developed in such a way to make it possible to predict the dissolution rate (being informed by the particle size distribution) which, in its turn, can be used as a surrogate to predict the USP2 dissolution curve. Subsequently, validation can be done by using this profile as input for PBPK platforms.

FORMULATION AND EVALUATION OF TRANSDERMAL PATCHES OF DROTAVERINE HYDROCHLORIDE USING MERCURY SUBSTRATE METHOD

Aim of the present investigation is to prepare sustained release transdermal patches of Drotaverine hydrochloride. Transdermal drug delivery has ability to bypass liver first pass metabolism and deliver the drug towards systemic circulation. Drotaverine hydrochloride is used to treat the spasticity as muscle relaxant. Mercury substrate method is utilized for formulation of Transdermal patches of Drotaverine Hydrochloride. Ethyl cellulose and Eudragit RL 100 were used to retard the drug release. Dibutyl phthalate used as plasticizer and Dichloromethane as a solvent system. Transdermal patches were evaluated for physical appearance, weight variation, drug content, folding endurance, Fourier-transform infrared spectroscopy (FTIR), Differential scanning colourimetry (DSC) and invitro drug release study. The DSC curve of transdermal patch (TDDS D3) shows a sharp endothermic peak at 208.17°C indicating crystalline structure. The dissolution curve shows that formulation TDDS D3 shows maximum drug release 83.57% at the end of 12 Hrs. For transdermal patches according to ‘r’ value, Korsmeyer- Peppas model was best suited for drug release but n value obtained from Kors Meyer- Peppa’s equation was within 0.5 -1.0 which indicates anomalous releases

Design and Characterization of HY-038 Solid Dispersions via Spray Drying Technology: In Vitro and In Vivo Evaluations.

The aim of this study was to prepare HY-038 solid dispersions (SDs) with single carrier at high drug loading and then forming a tablet to enhance solubility, dissolution, and bioavailability via spray drying technology. At the same time, we hope to develop a more convenient in vitro method to predict the absorption behavior of different formulations in vivo. Different solid dispersions, varying in drug/polymer ratios, were prepared. Infrared spectroscopy, differential scanning calorimetry, scanning electron microscope, and X-ray diffraction were used to perform solid-state characterizations of the pure drug and SDs. Contact angle of water, dissolution in pH = 6.8 phosphate buffer, and in vivo absorption in dogs were studied. As a result, solid-state characterization demonstrated the transformation of the crystalline HY-038 to an amorphous state in the solid dispersions, and the in vivo exposure followed with the trend of the dissolution curve combined with contact angle. Compared with the prototype formulation, the Cmax and AUC0-∞ of optimized formulation SD2 (HY-038-HPMCAS 3:1) increased by about 5 ~ 9 times at the same dose. More importantly, the SD2 formulation showed approximately linear increases in Cmax and AUC0-∞ as the dose increased from 50 to 100mg, while the prototype formulation reached absorption saturation at 50mg. SD2 (HY-038-HPMCAS 3:1) was selected as the best formulation for the downstream development.

Stabilization of the Metastable α-Form of Indomethacin Induced by the Addition of 2-Hydroxypropyl-β-Cyclodextrin, Causing Supersaturation (Spring) and Its Sustaining Deployment (Parachute).

The purpose of this study is to find that a small amount of 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) can produce a parachute effect on indomethacin (INM). From the examination of dissolution curves and concentration after several days, the supersaturation of INM was observed for the mixtures containing HP-β-CD at a molar ratio ≤ 0.5, and the sustained deployment of supersaturation was found not only in equimolar mixtures but also in mixtures with a shortage of HP-β-CD. In the solid state, it was compared the physical properties of INM/HP-β-CD mixtures using two different mixing methods and determined the stoichiometry of INM and HP-β-CD. Differential scanning calorimetry (DSC) revealed that the polymorphs of INM were converted by HP-β-CD into an amorphous state. Furthermore, X-ray powder diffraction (XRPD) and DSC-XRPD demonstrated that INM crystals from the INM/HP-β-CD mixture prepared from an EtOH solution were metastable. In conclusion, these phenomena may be considered the "spring" and "parachute" effects of mixtures with a shortage of HP-β-CD, as they depended on the presence of the metastable α-form of INM. The addition of 1/3 to 1/20 equivalents of HP-β-CD to INM enhanced INM solubility.

Effect of Surfactants and Polymers on the Dissolution Behavior of Supersaturable Tecovirimat-4-Hydroxybenzoic Acid Cocrystals.

(1) Background: Pharmaceutical cocrystals have attracted remarkable interest and have been successfully used to enhance the absorption of poorly water-soluble drugs. However, supersaturable cocrystals are sometimes thermodynamically unstable, and the solubility advantages present a risk of precipitation because of the solution-mediated phase transformation (SMPT). Additives such as surfactants and polymers could sustain the supersaturation state successfully, but the effect needs insightful understanding. The aim of the present study was to investigate the roles of surfactants and polymers in the dissolution-supersaturation-precipitation (DSP) behavior of cocrystals. (2) Methods: Five surfactants (SDS, Poloxamer 188, Poloxamer 407, Cremophor RH 40, polysorbate 80) and five polymers (PVP K30, PVPVA 64, HPC, HPMC E5, CMC-Na) were selected as additives. Tecovirimat-4-hydroxybenzoic (TEC-HBA) cocrystals were chosen as a model cocrystal. The TEC-HBA cocrystals were first designed and verified by PXRD, DSC, SEM, and FTIR. The effects of surfactants and polymers on the solubility and dissolution of TEC-HBA cocrystals under sink and nonsink conditions were then investigated. (3) Results: Both the surfactants and polymers showed significant dissolution enhancement effects, and most of the polymers were more effective than the surfactants, according to the longer Tmax and higher Cmax. These results demonstrate that the dissolution behavior of cocrystals might be achieved by the maintained supersaturation effect of the additives. Interestingly, we found a linear relationship between the solubility and Cmax of the dissolution curve for surfactants, while no similar phenomena were found in solutions with polymer. (4) Conclusions: The present study provides a basis for additive selection and a framework for understanding the behavior of supersaturable cocrystals in solution.

A Critical Overview of FDA and EMA Statistical Methods to Compare In Vitro Drug Dissolution Profiles of Pharmaceutical Products.

A drug dissolution profile is one of the most critical dosage form characteristics with immediate and controlled drug release. Comparing the dissolution profiles of different pharmaceutical products plays a key role before starting the bioequivalence or stability studies. General recommendations for dissolution profile comparison are mentioned by the EMA and FDA guidelines. However, neither the EMA nor the FDA provides unambiguous instructions for comparing the dissolution curves, except for calculating the similarity factor f2. In agreement with the EMA and FDA strategy for comparing the dissolution profiles, this manuscript provides an overview of suitable statistical methods (CI derivation for f2 based on bootstrap, CI derivation for the difference between reference and test samples, Mahalanobis distance, model-dependent approach and maximum deviation method), their procedures and limitations. However, usage of statistical approaches for the above-described methods can be met with difficulties, especially when combined with the requirement of practice for robust and straightforward techniques for data evaluation. Therefore, the bootstrap to derive the CI for f2 or CI derivation for the difference between reference and test samples was selected as the method of choice.

Disintegration and release kinetics of dry compacted urea composites: A formulation and process design study

The hydrolysis of conventional urea fertilizer accounts for a 50 % loss in the field, which results in atmospheric and water stream contamination due to the volatilization of greenhouse and ozone scavenger gases, and nitrate leaching, respectively. Fertilizer granule structural design can be a potential solution to minimize the field losses. Nonetheless, quantitative analysis of urea dissolution as affected by formulation and process design remains underexplored. In this study, urea and a binder in powder form were mixed at a fixed binder-solid ratio of 5 % (w/w) and compacted at different loads using a punch-die set on a standard material testing system. The binders tested to produce the binary mixtures were hydroxypropyl methylcellulose grade E5- HPMC, high molecular weight hydroxypropyl cellulose- HPC, gluten from wheat, and a mixture of xanthan and konjac gums. The total porosity, apparent diffusion, and dynamic contact angle profiles of the compacts were measured at ambient conditions. The hydrophilicity of the formulations with gums, attributable to their lower contact angle when compared with control samples, helps explain the fast in-matrix mass transfer. Based on Weibull distribution model analysis, all the dissolution curves followed either sigmoidal or exponential shape profiles. Within the formulations evaluated in this study, the synergism between densification and higher hydration capacity of formulations with gums ensured binder mobility and gelation at the solid-liquid interface. The results indicate that gel formation reduced solvation and dissolution, resulting in a delay of nutrient release. These findings will aid in the optimization of controlled-release fertilizer formulations for field crops and help understand the effect of binder physicochemical characteristics on the microstructure of granular fertilizers.

Roles of aqueous additives in the mass transfer process of water molecules in water/oil/water double emulsion droplets

Finding suitable aqueous additives to inhibit the mass transfer of water molecules in double emulsion droplets is beneficial for improving the surface quality of polymer shells. In this work, fluorobenzene/aqueous systems with polyvinyl alcohol (PVA) molecules and electrolyte ions were constructed by molecular dynamics simulation, which are typical water/oil (W/O) systems in actual fabrication processes of polymer shells. The interfacial mass transfer coefficients and equilibrium water solubility in fluorobenzene of various W/O systems were calculated by fitting the dissolution curves with a classical mass transfer model. The effects of polyvinyl alcohol additives on the diffusion process of water molecules at the fluorobenzene/water interface were investigated from the perspectives of thermodynamics and microscopic interface morphology. Furthermore, to avoid the inner surface defects of polymer shells caused by electrolyte ions osmosis, 1,3-butanediol molecules were proposed to replace ions as aqueous solutes, which also inhibited the diffusion of water molecules to fluorobenzene membrane.

A New Validation Methodology for In Silico Tools Based on X-ray Computed Tomography Images of Tablets and a Performance Analysis of One Tool.

In silico tools which predict the dissolution of pharmaceutical dosage forms using virtual matrices can be validated with virtual matrices based on X-ray micro-computed tomography images of real pharmaceutical formulations. Final processed images of 3 different tablet batches were used to check the performance of the in silico tool F-CAD. The goal of this work was to prove the performance of the software by comparing the predicted dissolution profiles to the experimental ones and to check the feasibility and application of the validation concept for in silico tools. Both virtual matrices based on X-ray micro-computed tomography images and designed by the software itself were used. The resulting dissolution curves were compared regarding their similarity to the experimental curve. The kinetics were analysed with the Higuchi and Korsmeyers–Peppas plot. The whole validation concept as such was feasible and worked well. It was possible to identify prediction errors of the software F-CAD and issues with the virtual tablets designed within the software.

Predicting Drug Release from 3D Printed Oral Medicines Based on the Surface Area to Volume Ratio of Tablet Geometry.

3D printing offers the advantage of being able to modify dosage form geometry, which can be exploited to modify release characteristics. In this study, we investigated the influence of the surface area to volume ratio (SA/V) to change and predict release profiles of 3D printed dosage forms. Geometries with varying SA/V and dosages were designed and printed, and drug dissolution was investigated. Three drug substances were used: pramipexole, levodopa (both BCS I) and praziquantel (BCS II). Two polymers were chosen as matrix formers: polyvinyl alcohol (water-soluble) and ethylene vinyl acetate (inert). Drug release was characterized using the mean dissolution time (MDT) and established equations that describe complete dissolution curves were applied. Predictions were validated with previously un-printed dosage forms. Based on an identified MDT-SA/V correlation, the MDT can be predicted with a deviation of ≤5 min for a given SA/V. Using correlations of fit parameters and SA/V, RMSEP values of 0.6–2.8% and 1.6–3.4% were obtained for the BCS I formulations and RMSEP values of 1.0–3.8% were obtained for the BCS II formulation, indicating accurate prediction over a wide range of dissolution profiles. With this approach, MDT and release profiles of dosage forms with a given SA/V can be precisely predicted without performing dissolution tests and vice versa, the required SA/V can be predicted for a desired release profile.

A multi-evaluating strategy for Weikangling capsules: Chemical profiling, fingerprinting combined with quantitative analysis, quantity transfer, and dissolution curve

Weikangling capsules (WKLCs), a Chinese patent medicine consisting of 8 Chinese drugs, have been widely used in clinic to treat gastrointestinal diseases for more than 30 years. The current “Chinese Pharmacopoeia” (2020 Edition, ChP2020) uses paeoniflorin content (≥ 1.0 mg per capsule) as the standard of quality control, but it is insufficient to evaluate the overall quality of WKLCs. An efficient and economic method for quality control is urgently needed to ensure the quality consistency and clinical effects of WKLCs. Herein, a systematic and reliable method for the rapid analysis of chemical components in WKLCs was established for the first time based on ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A total of 115 components covering 7 herbs in WKLCs were preliminarily identified by comparison with standard substances or literature. To evaluate the quality of 26 batches of WKLCs, a new method of fingerprinting combined with quantitative analysis was established, and 16 common peaks were selected to establish the fingerprint similarity model (similarity>0.90). Simultaneously, the contents of albiflorin, paeoniflorin, dactylorhin A, militarine, and glycyrrhizic acid were determined to be 0.82 ± 0.22, 2.09 ± 0.24, 1.15 ± 0.40, 3.73 ± 0.76 and 0.99 ± 0.20 mg/capsule, respectively. The transfer rates and dissolution curves of the five compounds were successfully detected in WKLCs, and the average transfer rates were 67.2%, 33.0%, 68.3%, 54.7%, and 33.7%, respectively. Notably, the dissolution profiles of different manufacturers presented remarkable differences in pH 1.2 hydrochloric acid solution. This method not only qualitatively identified the chemical components of Chinese patent medicines at the microlevel but also evaluated the quality consistency between batches at the macrolevel, which provided a comprehensive reference for the quality consistency of Chinese patent medicines between batches.

The association of anticoagulation therapy characteristics with left atrial thrombus lysis in patients with nonvalvular persistent atrial fibrillation

Purpose. The aim of this study was to reveal the effect of the duration and characteristics of anticoagulant therapy on the clot dissolution in the left atrial appendage (LAA) in patients with persistent atrial fibrillation (AF).Material and methods. The repeat transesophageal echocardiography was performed in 68 patients with persistent AF, because the thrombus was detected in the LAA during the first examination. Of these, 37 (54.4%) patients started or continued to receive warfarin and 31 (45.6%) patients continued to receive the direct oral anticoagulants. Transesophageal echocardiography was repeated after 3-5 weeks. One follow-up examination was for 53 patients, two follow-up examination was for 11 patients and three follow-up examination was for 4 patients. Cox regression analysis was performed to identify factors affecting the likelihood of clot dissolution and Kaplan-Meier survival analyses with log-rank tests were used to compare the clot dissolution time.Results. The chance of the LAA thrombus lysis is 50% after 35.0 ± 3.7 days of receiving anticoagulants. This time is reduced to 30.0 ± 1.4 days for small thrombus (no more than 18 mm), and it increases to 45.0 ± 7.4 days (p = 0.038) for large thrombus. The dissolution time of small thrombus depends on the characteristics of the treatment: the median of the dissolution curve is 24.0 ± 3.7 days when the patients received the direct oral anticoagulants, and the median of the dissolution curve is 40.0 ± 7.2 days (p = 0.009), if the patients received warfarin. The dependence of the dissolution time of large thrombus on the characteristics of treatment did not found.Conclusion. The LAA thrombus dissolution time in patients with atrial fibrillation depends on their size, and the dissolution time of small thrombi depends on the characteristics of anticoagulant therapy.

Phase Equilibria on the Reciprocal Quaternary System K+, Rb+ // Cl–, and Borate–H2O at T = 323.2 K and p = 94.77 kPa

The isothermal dissolution method was applied for the phase equilibrium experiment of the quaternary system K+, Rb+ // Cl–, and borate–H2O at T = 323.2 K and p = 94.77 kPa. The solubilities and refractive indices (nD) of the system were determined experimentally. The coexisting salts of the quaternary invariant points were identified using the X-ray diffraction (XRD) method. Based on the measured data, the stable phase diagram and the figures of water content and refractive index (nD) vs composition were plotted for this system at 323.2 K. The results show that the system belongs to a complex type with the formation of a solid solution [(K, Rb)Cl]. The stable phase diagram consists of three quaternary invariant points, seven isothermal dissolution curves, and five crystallization regions corresponding to KCl, RbCl, RbB5O6(OH)4·2H2O, K2B4O5(OH)4·2H2O, and [(K, Rb)Cl]. The size of the RbB5O6(OH)4·2H2O crystallization zone is the largest among the coexisting salts in the quaternary system, which means it is the most easily crystallized from the mixed solution containing potassium, rubidium, chloride, and borate.

PharmSD: A novel AI-based computational platform for solid dispersion formulation design

Solid dispersion is an effective way to improve the dissolution and oral bioavailability of water-insoluble drugs. To obtain an effective solid dispersion formulation, researchers need to evaluate a series of important properties of the designed formulation, including in vitro dissolution and physical stability of solid dispersion. It is usually time-consuming and labor-intensive to explore these properties by traditional experimental methods. However, the development of machine learning technology provides a powerful way to solve such problems. By using advanced machine learning algorithms, we established a series of robust models and finally formed a systematic strategy to assist the formulation design. Based on these works, we developed a new formulation prediction platform of solid dispersion: PharmSD. This platform provides efficient functionalities for the prediction of physical stability, dissolution type and dissolution rate of solid dispersion independently. Then, a virtual screening pipeline can be produced by considering those prediction results as a whole, which enables users to filter different kinds of drug-polymer combinations in various experimental situations and figure out which combination could form the best formulation. Moreover, it also provides two tools that enable researchers to evaluate the application domain of models and calculate the similarity of dissolution curves. PharmSD is expected to be the first freely available web-based platform that is fully designed for the formulation design of solid dispersion driven by machine learning. We hope this platform could provide a powerful solution to assist the formulation design in the related research area. It is available at: http://pharmsd.computpharm.org.

Analysis of Gene Mutation Types in 141 Cases of α-Thalassemia in Honghe Prefecture, Yunnan Province

To detecte the carrying rate, the type and distribution of α-Thalassemia gene mutation in Honghe Prefecture, Yunnan Province, and analyze the differences in average erythrocyte volume (MCV), mean erythrocyte hemoglobin content (MCH) and hemoglobin among different types of α-Thalassemia. The DNA samples from small cell hypochromic carriers or anemia patients and women of childbearing age who underwent hematological screening in The First People's Hospital of Honghe State was from 2015 to 2019 were enrolled and analyzed, and the mutation types and frequency of alpha-thalassemia positive rate were diagnosed by PCR reverse dot blot or PCR fluorescence dissolution curve. Among the 1 016 samples, 141(13.88%) of the patients were diagnosed as α-thalassemia. The α-thalassemia was subdivided into 3 types, silent (36.17%), minor (51.77%), and HbH disease (12.06%), and the MCV, MCH and HB levels were detected and showed a obvious decrease trend with significant difference (P < 0.05). The gene mutation types were 9 kinds, the deletion type gene was mainly --SEA (51.06%), followed by -α3.7/αα deletion (29.79%), the α- mutation type gene was mainly αcsα(3.55%). The absence of complex heterozygote was most common, which was 17 cases, accounting for 12.77%, mainly --SEA/-α3.7 (10.64%). The areas were mainly distributed in Mengzi (47.52%), followed by Jinping (17.02%). Ethnic groups were mainly distributed in Han nationality (49.65%), followed by Zhuang (15.60%), Yi (3.48%) and Dai (7.09%). The patients with double heterozygous mutation was slightly higher in Mengzi than that in Jinping County (4.26% vs 3.55%), the Dai (2.13%) showed Zhuang ethnic group (2.13%) had the relatively high incidence except the Hans, and showed the most serious anemia. Alpha-thalassemia in Honghe prefecture of Yunnan Province shows complex genetic diversity and significant genetic heterogeneity, and the mainly type of gene mutation is --SEA and --SEA/-α3.7, which is mainly distributed in Han, Zhuang and Dai ethnic groups in Mengzi, Jinping. The anemia index of HbH group is the most obvious, and it is significantly different from other groups.

Solid-Liquid Phase Equilibria in the Quaternary System (KCl + MgCl2 + K2B4O7 + MgB4O7 + H2O) at 308.15 K

Solubility data for the quaternary system (KCl + MgCl2 + K2B4O7 + MgB4O7 + H2O) is very important for the separation of potassium and boron from the salt lake brines in Qaidam Basin. The solubility of the quaternary system (KCl + MgCl2 + K2B4O7 + MgB4O7 + H2O) at T = 308.15 K and p = 0.1 MPa has been investigated experimentally with the method of isothermal dissolution equilibrium, and meanwhile physicochemical properties including density, refractive index, and pH value have been determined. In the phase diagrams of the quaternary system at 308.15 K, there are three invariant points, seven univariant isothermal dissolution curves, and five crystallization regions corresponding to KCl, MgCl2·6H2O, K2B4O7· 4H2O, Mg2B6O11·15H2O, and double salt KCl·MgCl2·6H2O, respectively. The density, refractive index and pH value of the quaternary system at 308.15 K present a regular variation with the increasing of Mg2+ concentration.

DISSOLUTION KINETIC OF MELOXICAM FROM HYDROPHILIC MATRIX-TYPE FILMS FOR TRANSDERMAL THERAPY

Taking into consideration the fact the transdermal administration of the active pharmaceutical ingredients can represent a therapeutic approach that increases the patient’s compliance, this study aims to evaluate the release of meloxicam (MX), a potent non-steroidal anti-inflammatory drug, incorporated in hydrophilic polymer-based matrices for transdermal therapeutic systems was studied. Three different formulations were realized by solvent casting method containing two types of hydroxypropyl methylcellulose (HPMCE5 with low viscosity and HPMC15000 with high viscosity) whose concentration was also varied. The drug release test was performed by Franz diffusion cell and the dissolution curves were analysed from a kinetical point of view by model dependent and model independent methods. Linearization by simple regression allowed the flux calculations of values that varied between 0.183 and 32.270 g/(cm2h). Based on the results obtained with the mathematical analysis, we can conclude that the MX release is influenced by the pH of the dissolution media and by the type and concentration of the matrix forming agent. Discrimination of model dependent mathematical models was done by the Akaike index with values between 49 and -62. The kinetic analysis of the MX releasing curves from the proposed formulations showed that Korsmeyer-Peppas was more suitable for the release characterisation of the active pharmaceutical ingredient from the transdermal therapeutic systems analysed.

Combined Effect of the Preparation Method and Compression on the Physical Stability and Dissolution Behavior of Melt-Quenched Amorphous Celecoxib.

In an earlier investigation, amorphous celecoxib was shown to be sensitive to compression-induced destabilization. This was established by evaluating the physical stability of uncompressed/compressed phases in the supercooled state (Be̅rziņš . Mol. Pharmaceutics, 2019, 16(8), 3678-3686). In this study, we investigated the ramifications of compression-induced destabilization in the glassy state as well as the impact of compression on the dissolution behavior. Slow and fast melt-quenched celecoxib disks were compressed with a range of compression pressures (125-500 MPa) and dwell times (0-60 s). These were then monitored for crystallization using low-frequency Raman spectroscopy when kept under dry (∼20 °C; <5% RH) and humid (∼20 °C; 97% RH) storage conditions. Faster crystallization was observed from the samples, which were compressed using more severe compression parameters. Furthermore, crystallization was also affected by the cooling rate used to form the amorphous phases; slow melt-quenched samples exhibited higher sensitivity to compression-induced destabilization. The behavior of the melt-quench disks, subjected to different compression conditions, was continuously monitored during dissolution using low-frequency Raman and UV/vis for the solid-state form and dissolution properties, respectively. Surprisingly the compressed samples exhibited higher apparent dissolution (i.e., higher area under the dissolution curve and initial celecoxib concentration in solution) than the uncompressed samples; however, this is attributed to biaxial fracturing throughout the compressed compacts yielding a greater effective surface area. Differences between the slow and fast melt quenched samples showed some trends similar to those observed for their storage stability.

Solid-liquid phase equilibria of the quinary system containing sodium, potassium, lithium, chloride and pentaborate ions at 298.15 K and 101.325 kPa

The solid–liquid phase equilibria of the quinary system (Li+, Na+, K+//Cl−, B5O8− - H2O) saturated with NaCl at 298.15 K and 101.325 kPa were investigated with the isothermal dissolution method. On the basis of experimental data, the dry-salt phase diagram, water-phase diagram and sodium-phase diagram in the quinary system were established for the first time. In this quinary dry-salt phase diagram, there are three invariant points corresponding to F1 (NaCl + KCl + LiCl·H2O + LiB5O8·5H2O), F2 (NaCl + KCl + LiB5O8·5H2O + KB5O8·4H2O) and F3 (NaCl + LiB5O8·5H2O + NaB5O8·5H2O + KB5O8·4H2O), seven isothermal dissolution curves, and five crystallization regions saturated with NaCl corresponding to LiCl·H2O, KCl, LiB5O8·5H2O, NaB5O8·5H2O, KB5O8·4H2O. The areas of crystallized regions decrease according to the order of NaB5O8·5H2O, KB5O8·4H2O, LiB5O8·5H2O, KCl, and LiCl·H2O, which all are saturated with sodium chloride. It was found that neither double salt nor solid solution was formed. In addition, the diagram of physicochemical properties including densities and refractive indices against J(B5O8−) was also established, and it shows that density and refractive index of the solution in the quinary system change regularly with the increasing of Jänecke index J(B5O8−) in the solution. These results on the phase diagram of the quinary system can supply a theoretical guide to separate and purify the valuable alkali pentaborates.

Quality Evaluation of Generic Oral Solid Preparations by Multiple Dissolution Curves

Quality Evaluation of Generic Oral Solid Preparations by Multiple Dissolution Curves